反相高效液相串联质谱法快速测定人血浆中齐拉西酮的浓度及临床应用

 目的建立测定人血浆中齐拉西酮浓度的反相高效液相串联质谱电喷雾检测法(LC-ESI-MS/MS)。方法以迪马公司C18反相柱(Dialmonsil C₁₈ column,4.6 mm×150 mm,5μm)为色谱柱,流动相为甲醇-5 mmol·L^-1甲酸铵(90∶10),流速为1 mL·min^-1,柱温:25℃,以醋酸乙酯-二氯甲烷(4∶1)为提取剂。样品经电喷雾离子源正离子化后,通过三重四级杆串联质谱仪,采用选择反应监测(SRM)对齐拉西酮(m/z 413.2→194.1)和内标替米沙坦(m/z 515.3→276.2)进行测定,并用此法测定20例患者稳态血药浓度。结果齐拉西酮的高(250μg·L^-1)、中(100μg·L^-1)、低(10μg·L^-1)3个质量浓度的平均回收率分别为100.33%,94.31%和104.70%,日内(n=5)、日间(n=3)RSD均小于15%;分析方法的最低定量限为5μg·L^-1。线性范围为:5～500μg·L^-1,回归方程为F=1.367 7ρ-0.024 5,r=0.999(n=7)。结论该方法灵敏、准确、简单、快速,可用于临床血浓监测和药动学研究。

Study on Rapid Determination of Ziprasidone in Plasma by LC-ESI-MS/MS and Its Clinical Application

OBJECTIVE To develop a LC-ESI-MS/MS method for ziprasidone assay inplasma.METHODS Ziprasidone was extracted with ethyl acetate-dichiloromethane(4∶1).The residues were separated on a Dikma Diamonsil C₁₈ column,4.6 mm×150 mm,5 μm) with the mobile phase consisting of methanol:water with 5 mmol·L^-1 ammonium formate(90∶10).A agilent 6410 triple quad mass spectrometer system equipped with an electrospray ionization ion-trap source was used as the detector and operated in the positive ion mode.Selected reaction monitoring(SRM) using the precursor to product ion combinations of m/z 413.2 →194.1 and m/z 515.3→276.2 was performed to detect ziprasidone and the internal standard,respectively.The method was used to evaluate clinical application for 20 patients after multiple oral doses ziprasidone hydrochloride tablets.RESULTS The average recoveries for ziprasidone were 100.33%,94.31% and 104.70%,respectively.The within-day(n=5) and between-day(n=3) precision of variation were less than 15%.The calibration curves for ziprasidone had good linearity(r=0.999,n=7)over the range of 5-500 μg·L^-1.The limits of quantitation for ziprasidone was 5 μg·L^-1.CONCLUSION The method provides a sensitive,accurate,precise and reliable analytical procedure for clinical monitoring of ziprasidone plasma and its phamacokinetic studies.